title: Fibrinopeptide A changes during remission induction treatment with L-asparaginase in acute lymphoblastic leukemia: evidence for activation of blood coagulation.
abstract: L-Asparaginase, a widely used antileukemic agent, inhibits liver protein synthesis leading to hypofibrinogenemia and hypoprothrombinemia together with a severe reduction of antithrombin III and protein C. An increased risk of thrombosis has been reported in leukemic patients treated with this agent. We measured fibrinopeptide A (FPA) changes in 14 patients with acute lymphoblastic leukemia during induction remission treatment with a protocol including L-Asparaginase (10,000 U/m2/daily intravenous for 14 days). At diagnosis, 9/14 patients had FPA level above upper limit of normal range (mean = 4.1 ng/ml). After two days of therapy, FPA rose to 5.2 ng/ml and thereafter showed a slight increase throughout. Antithrombin III, protein C and fibrinogen dropped to its nadir on day 6 and 9. However, the ratio FPA/fibrinogen on a molar basis showed a three-fold increase during this days, demonstrating that the thrombin-dependent consumption of fibrinogen was also increased. In conclusion, our data show that activation of blood coagulation occurs in concomitance with the hemostatic derangement caused by L-Asparaginase. Replacement therapy with the recently available antithrombin III concentrates may be worthy of a clinical trial to test its effectiveness in preventing the thrombotic phenomena reported in these patients.
authors.affiliation: Department of Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: E
authors.initials: E
authors.lastname: Dini
mesh_terms: D000293:Adolescent; D000328:Adult; D001215:Asparaginase / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology; D002648:Child; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012074:Remission Induction; D013917:Thrombin / Q000378:metabolism / Q000502:physiology
chemical_list: D015415:Biomarkers; D005344:Fibrinopeptide A; D005340:Fibrinogen; D013917:Thrombin; D001215:Asparaginase